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The Journal of Neuroscience, November 25, 2009, 29(47):14812-14819; doi:10.1523/JNEUROSCI.3609-09.2009
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Behavioral/Systems/Cognitive
Functional Variation of the Dopamine D2 Receptor Gene Is Associated with Emotional Control as well as Brain Activity and Connectivity during Emotion Processing in Humans
Giuseppe Blasi,1 Luciana Lo Bianco,1 Paolo Taurisano,1 Barbara Gelao,1 Raffaella Romano,1 Leonardo Fazio,1,5 Apostolos Papazacharias,1 Annabella Di Giorgio,1 Grazia Caforio,1 Antonio Rampino,1 Rita Masellis,1 Audrey Papp,2 Gianluca Ursini,1,3 Lorenzo Sinibaldi,3,4 Teresa Popolizio,5 Wolfgang Sadee,2 andAlessandro Bertolino1,5 1Psychiatric Neuroscience Group, Department of Neurological and Psychiatric Sciences, University of Bari, 70124 Bari, Italy, 2Program in Pharmacogenomics, Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio 43215, 3Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mendel Institute, 00198 Rome, Italy, 4Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy, and 5Department of Neuroradiology, IRCCS "Casa Sollievo della Sofferenza," 71013 San Giovanni Rotondo, Italy
Correspondence should be addressed to Dr. Alessandro Bertolino, Dipartimento di Scienze Neurologiche e Psichiatriche, Università degli Studi di Bari, Piazza Giulio Cesare, 9, 70124 Bari, Italy. Email: a.bertolino{at}psichiat.uniba.it
Personality traits related to emotion processing are, at least in part, heritable and genetically determined. Dopamine D2 receptor signaling is involved in modulation of emotional behavior and activity of associated brain regions such as the amygdala and the prefrontal cortex. An intronic single nucleotide polymorphism within the D2 receptor gene (DRD2) (rs1076560, guanine > thymine or G > T) shifts splicing of the two protein isoforms (D2 short, mainly presynaptic, and D2 long) and has been associated with modulation of memory performance and brain activity. Here, our aim was to investigate the association of DRD2 rs1076560 genotype with personality traits of emotional stability and with brain physiology during processing of emotionally relevant stimuli. DRD2 genotype and Big Five Questionnaire scores were evaluated in 134 healthy subjects demonstrating that GG subjects have reduced "emotion control" compared with GT subjects. Functional magnetic resonance imaging in a sample of 24 individuals indicated greater amygdala activity during implicit processing and greater dorsolateral prefrontal cortex (DLPFC) response during explicit processing of facial emotional stimuli in GG subjects compared with GT. Other results also demonstrate an interaction between DRD2 genotype and facial emotional expression on functional connectivity of both amygdala and dorsolateral prefrontal regions with overlapping medial prefrontal areas. Moreover, rs1076560 genotype is associated with differential relationships between amygdala/DLPFC functional connectivity and emotion control scores. These results suggest that genetically determined D2 signaling may explain part of personality traits related to emotion processing and individual variability in specific brain responses to emotionally relevant inputs.
Received July 26, 2009; revised Sept. 16, 2009; accepted Oct. 13, 2009.
Correspondence should be addressed to Dr. Alessandro Bertolino, Dipartimento di Scienze Neurologiche e Psichiatriche, Università degli Studi di Bari, Piazza Giulio Cesare, 9, 70124 Bari, Italy. Email: a.bertolino{at}psichiat.uniba.it
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